Elsevier

Ophthalmology

Volume 120, Issue 10, October 2013, Pages 2042-2050
Ophthalmology

Original article
Incidence and Progression of Geographic Atrophy: Observations from a Population-based Cohort

https://doi.org/10.1016/j.ophtha.2013.03.029Get rights and content

Purpose

To examine early age-related macular degeneration (AMD) lesion characteristics and risk factors associated with the long-term development and progression of geographic atrophy (GA).

Design

Population-based cohort.

Participants

Of 3654 participants aged ≥49 years in the Blue Mountains Eye Study, 75.8%, 76.7%, and 56.1% of survivors attended the 5-, 10-, and 15-year follow-up examinations, respectively.

Methods

Retinal photographs were taken at each visit. Incident GA was confirmed using a side-by-side grading method. Computer planimetry was used to measure the area involved by GA. Fast and slow/normal progression rates were defined as GA area enlargement by ≥2 and <2 mm2/year, respectively. Incident GA was estimated using the Kaplan–Meier product-limit method. Early AMD lesion characteristics were assessed for association with GA incidence using eye-specific data and generalized estimating equation models adjusting for age, current smoking, and presence of risk alleles of the complement factor H (CFH) or age-related maculopathy susceptibility 2 (ARMS2) genes, genotyped or imputed using genome-wide scan data.

Main Outcome Measures

Incidence and progression of GA.

Results

By excluding 41 subjects with GA at baseline, of 2503 participants at risk of GA, incident pure GA (without coexisting neovascular AMD lesions) was confirmed in 57 participants, with a 15-year incidence of 3.6%. Baseline early AMD lesion characteristics associated with GA incidence included drusen type (soft indistinct: odds ratio [OR], 59.0; 95% confidence interval [CI], 20.4–171.0; reticular drusen: OR, 13.9; 95% CI, 4.0–47.6); drusen location within a 500-μm radius of the fovea (OR, 15.1; 95% CI, 7.4–30.8); drusen area greater than 375 μm in diameter (OR, 10.1; 95% CI, 4.0–25.6); presence of retinal pigment epithelial depigmentation (OR, 9.0; 95% CI, 4.1–19.8); or hyperpigmentation (OR, 12.0; 95% CI, 6.1–23.5), referenced to subjects with no or hard drusen only. Fast progression was more frequent among current smokers at baseline, subjects with the CFH or ARMS2 risk genotypes, and pseudophakic eyes.

Conclusions

Early AMD lesion characteristics (type, location, area involved) were strongly associated with higher long-term risk of developing GA independent of age, smoking, and AMD genetic susceptibility from the CFH or ARMS2 genes. Known AMD risk factors also were more frequently present among quickly progressing GA cases.

Financial Disclosure(s)

Proprietary or commercial disclosure may be found after the references.

Section snippets

Study Population

The BMES is a population-based cohort study of vision and eye disease in persons aged 49 years or older residing in the Blue Mountains region west of Sydney, Australia.18, 19 The baseline study recruited and examined 3654 participants (82.4% of those eligible) between 1992 and 1994 (BMES I). Of these, 2334 participants (75.8% of survivors) attended the 5-year follow-up examinations (1997–1999; BMES II). The 10-year (2002–2004; BMES III) and 15-year (2007–2009; BMES IV) follow-up examinations

Results

Of 3654 baseline participants, 2572 had been followed-up at least once since the baseline examination. Of these, 68 participants had late AMD at baseline or developed neovascular AMD by first follow-up after baseline (and were thus not at risk of developing GA), and 1 participant had ungradable photographs at all visits. This left 2503 participants included in the assessment of GA incidence. Table 1 presents baseline characteristics of the BMES participants with incident GA and without any late

Discussion

In this older Australian cohort, we found an overall 3.6% incidence of pure GA over 15 years. Common AMD risk factors, including increasing age, history of smoking, genetic risk from the CFH and ARMS2 alleles, and regular fish consumption, were associated with long-term incidence of pure GA. In addition, early AMD lesion characteristics strongly predicted risk of GA independent of the known risk factors discussed earlier. We also found that fast progression of GA was more likely to occur in

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Financial Disclosure(s): The author(s) have made the following disclosure(s): P.M. is a consultant for Novartis and Bayer. The other authors have no proprietary or commercial interest in any materials discussed in this article.

Supported by the National Health and Medical Research Council, Australia (Grants 974159, 211069, 457349). The National Health and Medical Research Council had no role in the design or conduct of this research.

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